Microneedles for minimally invasive drug delivery

ABSTRACT

The present invention provides a microneedle incorporating a base that is broad relative to a height of the microneedle, to minimize breakage. The microneedle further includes a fluid channel and a beveled non-coring tip. Preferably arrays of such microneedles are fabricated utilizing conventional semiconductor derived micro-scale fabrication techniques. A dot pattern mask is formed on an upper surface of a silicon substrate, with each orifice of the dot pattern mask corresponding to a desired location of a microneedle. Orifices are formed that pass completely through the substrate by etching. A nitride pattern mask is formed to mask all areas in which a nitride layer is not desired. A nitride layer is then deposited on the bottom of the silicon substrate, on the walls of the orifice, and on the top of the silicon substrate around the periphery of the orifice. The nitride layer around the periphery of the orifice is offset somewhat, such that one side of the orifice has a larger nitride layer. Anisotropic etching is used to remove a substantial portion of the substrate, creating a plurality of angular, blunt, and generally pyramidal-shaped microneedles. A subsequent removal of the nitride layer, followed by an isotropic etching step, softens and rounds out the blunt angular microneedles, providing generally conical-shaped microneedles. The uneven nitride layer adjacent the orifice ensures that the microneedles will include a beveled tip. Such microneedle arrays are preferably incorporated into handheld diagnostic and drug delivery systems.

FIELD OF THE INVENTION

[0001] The present invention generally relates to apparatus used fordelivering medicinal fluid to a patient, and a method for fabricatingsuch apparatus, and more specifically, to apparatus having an array ofmicroneedles for transdermally delivering a medicinal fluid to a patientin a minimally invasive manner, and a method for fabricating the same.

BACKGROUND OF THE INVENTION

[0002] There are many medical conditions and procedures in which it isnecessary to either deliver a drug to a patient across the dermalbarrier, or to withdraw a sample of blood or tissue from a patientacross the dermal barrier. A hypodermic needle-tipped syringe is mostcommonly employed for transcutaneously delivering a medicinal fluid to apatient. A significant segment of the population considers receiving aninjection delivered with a hypodermic needle to be a painful andunpleasant experience. Although most individuals are required to receivesuch injections only a few times over the course of their lifetime,those suffering from medical conditions such as diabetes will requiremuch more frequent injections.

[0003] The size of the needle used with common hypodermic syringes istypically a few millimeters in length. These needles, which are referredto as macro-needles, have a relatively large diameter compared to thesize of a biological cell. The pain associated with a needle piercing adermal layer is clearly related to the diameter of the needle. In anattempt to decrease the level of pain an individual experiences whenreceiving an injection, the use of microneedles has been investigated.Microneedles can be fabricated in lengths that enable the dermal barrierto be penetrated sufficiently deep for drug delivery to occur, but notso deep as to stimulate nerves that cause pain and discomfort.

[0004] As an alternative to macro-needles, microneedles having adiameter measured in micrometers have been developed. The reduced sizedecreases discomfort and pain to the patient. Research has demonstratedthat silicon microprobes with cross sections on the order of tens ofmicrometers can penetrate living tissue without causing significanttrauma. (K. Najafi, K. D. Wise and T. Mochizuki, “A High-YieldIC-Compatible Multichannel Recording Array,” IEEE Micro Trans. onElectron Devices, vol. ED-32, pp. 1206-1211, July 1985.)

[0005] Several different types of microneedles have been developed.Glass pipettes have been used to fabricate microneedles with a diameterof approximately 20 μm. These microneedles can be formed by heating arelatively large diameter glass pipette and stretching the pipette untilits diameter is reduced to about 20 μm. Glass microneedles of this sizecan be used to inject and withdraw fluids from a single cell. However,the stretching technique employed to produce the microneedle is rathercrude, and it is difficult to accurately and reproducibly control thesize of a microneedle fabricated in this manner. Furthermore, suchmicroneedles are extremely fragile.

[0006] U.S. Pat. No. 5,457,041 discloses an array of microneedlesextending outwardly from a supporting substrate and having tip portionsshaped and dimensioned to both carry a biologically active substance andto pierce and penetrate into target cells within tissue, so that thebiological substance is transferred from the tip portion and depositedwithin the target cells. The array of microneedles is fabricated usingsilicon wafers and photolithographic-based etching techniques. Theresult is an array of solid microneedles. Any biologically activesubstance to be delivered by these needles must be loaded onto the tipsof the microneedles to effect delivery. Such tip loading is noteffective to deliver a precisely metered dose of a biologically activesubstance. Generally, medical treatment methodologies that include thetransdermal injection of drugs into a patient require preciselycontrolling the amount of drug delivered. Delivery of too little amountsof a drug may not effect the desired result, and too much of the drugcan have serious, possibly even fatal, consequences. Therefore, it wouldbe desirable to provide a microneedle-based drug delivery system thatoffers better control over the dosage of the drug delivered by themicroneedles, than this prior art technique.

[0007] U.S. Pat. No. 5,591,139 discloses a different type ofsilicon-based microneedle. Rather than producing an array of needlesthat extend outwardly from a substrate, this patent disclosesfabricating a microneedle that extends parallel to the plane of asilicon substrate. Using a combination of masking and etchingtechniques, a hollow microneedle is formed, which includes an interfaceregion and a shaft. A shell defining an enclosed channel forms theshaft, which has ports to permit fluid movement. The interface regionincludes microcircuit elements that can be used to providemicro-heaters, micro-detectors or other micro-devices on themicroneedle. While a microneedle incorporating a fluid path is extremelyuseful, the shaft of the microneedle disclosed in this patent isrelatively thin and narrow, and breakage is a concern. Furthermore,incorporation of electronic circuitry in the interface region increasesthe costs and complexity of these microneedles, and such circuitry isnot required for all microneedle applications. Finally, using andmanipulating an individual microneedle, as opposed to an array ofmicroneedles, presents other challenges.

[0008] A more recent patent directed to microneedle arrays is U.S. Pat.No. 6,033,928, which discloses an array of semiconductor microneedles,each having a diameter sufficiently small to exhibit quantum effects.These semiconductor microneedle arrays can be used to provide asemiconductor apparatus with high information-processing functionalityand are fabricated by forming a silicon dioxide film on a siliconsubstrate. Hemispherical grains made of silicon, each having anextremely small diameter, are then deposited on the film by vapordeposition. After annealing the hemispherical grains, the silicondioxide film is etched using the hemispherical grains as a first dottedmask, thereby forming a second dotted mask comprising the silicondioxide film. The resulting second dotted mask is used to etch thesilicon substrate to a specified depth, thereby forming an aggregate ofsemiconductor microneedles. Note that drug delivery applicationsgenerally do not require a microneedle that is a semiconductor.

[0009] In consideration of the prior art discussed above, it would bedesirable to provide an array of microneedles that each incorporate afluid channel through which a controlled volume of fluid can bedelivered. Preferably, such microneedle arrays would be designed tominimize the breakage of individual needles within the array, a commonproblem with prior art microneedles. It would be desirable to provide amethod for fabricating such an array of microneedles that utilizesconventional micro-scale fabrication techniques, such that the size ofthe microneedles can be accurately and reproducibly controlled. It wouldbe further desirable to provide a microneedle-based drug delivery systemthat offers full control over the dosage of the drug delivered by themicroneedles. The prior art does not disclose or suggest such anapparatus or method.

SUMMARY OF THE INVENTION

[0010] In accord with the present invention, a hollow microneedle fortranscutaneously conveying a fluid is defined. The microneedle has agenerally conical-shaped body, with a beveled, non-coring tip that isable to pierce tissue and a broad base. A fluid channel extends throughthe body connecting the broad base in fluid communication with the tip.

[0011] Preferably, the height of the microneedle, which is the distancefrom the broad base to the tip, is the about the same or substantiallyless than a width of the broad base. The microneedle is fabricated froma silicon-based substrate, using semiconductor fabrication techniques.

[0012] In one embodiment, an array of hollow microneedles arefabricated. The array includes a substrate with at least one inlet and aplurality of outlets in fluid communication with the at least one inlet.The microneedles extend outwardly from the substrate, each beingproximate to an outlet through the substrate. Each microneedle in thearray is generally configured as noted above.

[0013] Another aspect of the present invention is directed to a methodof manufacturing a hollow microneedle. The method includes the steps ofproviding a substrate; forming an orifice within the substrate, suchthat the orifice passes completely through the substrate; and removing asubstantial portion of the substrate, leaving a remainder. The remainderis disposed around the orifice and is generally conical in shape, sothat the orifice is disposed generally along a central axis of theconical shape. The step of removing a substantial portion of thesubstrate preferably bevels a tip of the conical shape.

[0014] In a preferred method, the substrate is silicon or polysilicon,and conventional semiconductor fabrication methods are employed for thefabrication process. For example, to form an orifice, a first mask isformed such that only portions of the substrate corresponding to adesired location of the orifice are exposed. The orifice is then etched,and the first mask removed. A second mask is formed and a nitride layeris deposited on unmasked areas. The second mask is then removed, and thesubstrate is etched to remove a substantial portion. The step of etchingthe substrate preferably comprises the step of performing an anisotropicetch, and then performing an isotropic etch.

[0015] Another aspect of the present invention is directed toward amethod of manufacturing an array of hollow microneedles, which isgenerally consistent with the method discussed above.

[0016] Yet another aspect of the present invention is directed to aminimally invasive diagnostic system for sampling and analyzing abiological fluid from a patient. Such a system includes a handhelddiagnostic unit, a disposable cartridge for obtaining a sample of thebiological fluid, and a sensor that when in contact with the sample,produces a signal indicative of a characteristic of the biologicalfluid. The handheld diagnostic unit includes a housing, a processor, adisplay electrically coupled to the processor, a keypad electricallycoupled to the processor, and a memory electrically coupled to theprocessor. The disposable cartridge includes a housing and an array ofmicroneedles and is adapted to bring the sample into contact with thesensor.

[0017] Preferably, the memory stores machine instructions that whenexecuted by the processor, cause it to perform a diagnostic procedureand indicate a result of the diagnostic procedure to a user on thedisplay. In one embodiment, the diagnostic procedure determines a levelof glucose in the biological fluid. Preferably, the housing includes areceptacle having a size and shape adapted to receive the disposablecartridge, such that when the cartridge is inserted into the receptacle,the sample of biological fluid is brought into contact with the sensor,and the sensor is electrically connected to the processor. In oneembodiment, the sensor is disposed in the disposable cartridge, while inanother embodiment, the sensor is disposed in the housing of thehandheld diagnostic unit.

[0018] A still further aspect of the present invention is directedtoward a minimally invasive drug delivery system for infusing amedicinal fluid into a patient. This system includes a handheld controlunit, a disposable cartridge for delivering the medicinal fluid to thepatient, and a fluid line connecting the handheld unit to the disposablecartridge. The handheld unit includes a housing, a processor, a displayelectrically connected to the processor, a keypad electrically connectedto the processor, a memory electrically connected to the processor, amedicinal fluid reservoir controllably connected to the processor, amedicinal fluid outlet in fluid communication with the medicinal fluidreservoir, and an actuator that develops a pressure to force themedicinal fluid through the medicinal fluid outlet so that it is infusedinto a patient. The disposable cartridge includes a housing and an arrayof microneedles through which the medicinal fluid is infused into thepatient.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

[0019] The foregoing aspects and many of the attendant advantages ofthis invention will become more readily appreciated as the same becomesbetter understood by reference to the following detailed description,when taken in conjunction with the accompanying drawings, wherein:

[0020] FIGS. 1A-1D are side elevational views of several prior artmicroneedles;

[0021]FIG. 2 is an isometric view of an array of prior art microneedlesthat can be fabricated using techniques common to semiconductorfabrication;

[0022]FIG. 3A is a side elevational view of a hollow microneedle inaccord with the present invention;

[0023]FIG. 3B is a plan view of the hollow microneedle of FIG. 3A;

[0024]FIG. 4 is a side elevational view of another embodiment of ahollow microneedle in accord with the present invention, in which a baseof the microneedle is substantially wider than a height of themicroneedle;

[0025]FIG. 5 is schematic view of a plurality of microneedles formed asan array, each microneedle in the array being like that illustrated inFIGS. 3A-3B;

[0026]FIG. 6 is a flow chart illustrating the sequence of logical stepsused to fabricate a hollow microneedle in accord with the presentinvention;

[0027] FIGS. 7A-7J are schematic representations of the sequence oflogical steps used to fabricate a hollow microneedle in accord with theflow chart of FIG. 6;

[0028]FIG. 8 is a schematic representation of a handheld diagnosticsystem that utilizes an array of microneedles in accord with the presentinvention;

[0029]FIG. 9 is a block diagram showing the functional elements of thehandheld diagnostic system of FIG. 8;

[0030]FIG. 10 is a partially exploded view showing a disposablecartridge that includes a microneedle array for use in the handhelddiagnostic system of FIG. 8;

[0031]FIG. 11 is a side elevational view of the microneedle array usedin the disposable cartridge of FIG. 9;

[0032]FIG. 12 is a schematic representation of a handheld drug deliverysystem that utilizes an array of microneedles in accord with the presentinvention;

[0033]FIG. 13 is a block diagram showing the functional elements of thehandheld drug delivery system of FIG. 12;

[0034]FIG. 14 is a partially exploded view of a disposable cartridgethat incorporates a microneedle array for use in the handheld drugdelivery system of FIG. 12;

[0035]FIG. 15 is a side elevational view of the microneedle array usedin the disposable cartridge of FIG. 14;

[0036]FIG. 16 is a schematic representation of a portion of amicroneedle element for use in the handheld drug delivery system of FIG.12, illustrating a fluid path within the element; and

[0037]FIG. 17 is a schematic representation of a drug reservoir for usein the handheld drug delivery system of FIG. 12, illustrating aself-sealing membrane, two actuators, and a sub-micron filter.

DESCRIPTION OF THE PREFERRED EMBODIMENT

[0038] Prior Art Microneedles

[0039] Before discussing the present invention, it will be helpful toconsider several examples of prior art microneedles, generally withreference to FIGS. 1A and 1B. FIG. 1A shows a generally conically-shapedmicroneedle 10, having a width W, measured along its base, and a heightH, measured from the base to the tip of the microneedle. Note that widthW is substantially less than height H of microneedle 10, and that widthW of the base corresponds to the diameter of microneedle 10 at its base.

[0040] A prior art microneedle (like microneedle 10) having a base whosewidth is approximately 30 μm and whose height is approximately 150 μmhas been disclosed on the World Wide Web at the addresshttp://mems.mirc.gatech.edu/research/biomed.html. Similarly, amicroneedle having a base with a width ranging from 0.5 μm to 10 μm, anda height of approximately 100 μm is described in U.S. Pat. No.4,969,468. This patent specifically teaches that the ratio of the heightof the microneedle to the width of the base of the microneedle should beon the order of 10 to 1, resulting in a relatively slender microneedle.U.S. Pat. No. 5,457,041 discloses microneedles whose width at the basevaries from 0.5 μm to 3.0 μm, and which are 10 μm to 25 μm tall. Each ofthese three sources thus disclose prior art microneedles whose heightexceeds the width of their base by a ratio of at least 8:1.

[0041]FIG. 1B illustrates a generally cylindrically-shaped prior artmicroneedle 12, whose height H also substantially exceeds its width W,measured at its base. U.S. Pat. No. 6,033,928 discloses a microneedleshaped like microneedle 12, having a base whose width ranges from 0.002μm to 0.05 μm, and whose height ranges from 0.5 μm to 2 μm. Thus,generally cylindrical microneedle 12 in the prior art have a height towidth ratio of at least 4:1.

[0042] The microneedles of the prior art generally are fabricated of asilicon-based material using conventional semi-conductor fabricationtechniques. A prior art microneedle array 18 shown in FIG. 2incorporates a plurality of prior art microneedles 10 from FIG. 1A.While other microneedles and arrays are disclosed in the prior art,their shape (height to base) characteristics are generally similar tothose illustrated in FIGS. 1A, 1B, and to those shown in FIG. 2. Priorart microneedles generally tend to be slender “spike” orcylindrically-shaped structures whose height is substantially greaterthan their width at the base.

[0043] Microneedle of the Present Invention

[0044]FIG. 3A illustrates a microneedle 20 in accord with the presentinvention. In contrast to the prior art microneedles discussed above,microneedle 20 has a base whose width W is substantially equivalent toits height H. In one embodiment, the width and height are about 100 μm;however, it should be noted that this example is simply exemplary and isnot intended to be limiting on the scope of the present invention.Microneedle 20 further incorporates a fluid channel 24 and a beveled,non-coring tip 25. FIG. 3B clearly shows that fluid channel 24 passescompletely through the microneedle. Note that a ratio of height H towidth W of microneedle 20 is substantially 1:1, whereas the microneedlesof the prior art have height-to-width ratios ranging from 4:1 to 10:1.By insuring that the microneedles in the present invention have a basethat is broad with respect to their height, a stronger microneedle, thatis less prone to breakage, is provided.

[0045]FIG. 4 illustrates a second embodiment of a microneedle in accordwith the present invention. Microneedle 22 incorporates a base whosewidth W exceeds its height H, i.e., its width W is approximately twiceits height H. In one embodiment, the width W is about 100 μm, while theheight H is about 50 μm, providing a height to width ratio of about 1:2.However, it should be similarly noted that the dimensions of 100 μm and50 μm are simply exemplary, and are not intended to be limiting on thescope of the present invention. A key feature of microneedle 22 is thatits ratio of height-to-width is less than 1:1, thus microneedle 22 has abase that is wider than its height. Microneedle 22 further incorporatesfluid channel 24′, and non-coring tip 25′.

[0046]FIG. 5 illustrates a microneedle array 26 of a plurality ofmicroneedles 20. Each microneedle 20 in the array includes fluid channel24 and non-coring tip 25, and each microneedle 20 has a height to widthratio of approximately 1:1.

[0047] Fabrication of Microneedle Array

[0048] A flowchart 28 in FIG. 6 illustrates the sequence of logicalsteps used to fabricate a microneedle needle array in accord with thepresent invention. FIGS. 7A-7I illustrate cross-sectional views of asubstrate material during the corresponding process steps in flowchart28, while FIG. 7J illustrates a finished microneedle.

[0049] It is anticipated that photolithography and other techniquesdeveloped for use in the semiconductor fabrication industry can bebeneficially employed in fabricating individual microneedles and arraysof microneedles in accord with the present invention. Thus, it isanticipated that silicon will be a preferred substrate, although othersubstrates, such as germanium, that can be manipulated using relatedtechniques, might also be used. In general, an array containing aplurality of broad base microneedles is preferably manufactured in abatch process, following steps somewhat like those used in semiconductormanufacturing processes. Accordingly, a silicon substrate will typicallycomprise a four-, six-, or eight-inch silicon wafer on which a pluralityof different microneedle arrays are fabricated at a time. However, forsimplicity, fabrication of only a single microneedle is illustrated inFIGS. 7A-7J. In addition, it will be understood that the various layerscomprising the microneedle are very thin, but for clarity, thedimensions of these layers as shown in the Figures are much exaggerated.

[0050] The following etching techniques are expected to be useful infabricating microneedles in accord with the present invention. AReactive Ion Etching (RIE) process is used to preferentially etchsilicon oxide, silicon nitride, or a silicon substrate. For thispurpose, a typical system includes a parallel plate reactive ion etchingconfiguration with a 5 inch quartz electrode, and a 1 KW, 15 MHz radiofrequency (RF) generator. Such a system can include a plurality of massflow controllers, a throttle valve and a controller (to maintainconstant pressure), and a high rate turbomolecular vacuum pump. RIE canbe used to remove layers such as polyimide, silicon nitride, or siliconoxide from silicon substrates such as wafers, wafer pieces, orindividual chips. Well known processes are available to etch siliconoxide and nitride (e.g., using carbon tetrafluoride, CF₄), to etchsilicon oxide preferentially to silicon nitride (using CF₄ andfluoroform, CHF₃), and to etch silicon preferentially to silicon oxide(using silicon hexafluoride, SF₆).

[0051] A commercially available system such as that described above isthe Cooke Vacuum Corporation, Model C71/3 Plasma System. Etch rates formost materials are 400-600 angstroms/minute. Etch rates for siliconoxide can be controlled to about +/−3%. The RF Frequency of the Cookesystem is 14.56 MHz, and the RF power is variable, up to 1000 watts.Process pressures can range from less than 50 to more than 1000 mtorr.The upper and lower electrodes, which are quartz, are closed-circuitliquid cooled. Multiple gas mixing is available at the manifold.

[0052] In addition to RIE, wet etching can also be beneficially employedto perform the etching required to fabricate microneedles in accord withthe present invention. Wet etching is a technique that utilizes liquidchemicals to remove materials surrounding a device or to delayer thinfilms from the surface of a substrate. This technique involves immersionof the device or substrate in a pure chemical or chemical mixture for agiven amount of time. The time required is dependent on the compositionand thickness of the layer to be removed, as well as the etchant andtemperature. A succession of chemicals may be required to removealternate layers on a device or substrate.

[0053] Wet etching can be used to remove organic materials, silicons,polyimides, metallization, polysilicon, or silicon oxide and siliconnitride layers. A few of the many chemicals available for etchinginclude: hydrofluoric acid, hydrochloric acid, sulfuric acid, nitricacid, phosphoric acid, acetic acid, hydrogen peroxide, chromiumtrioxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, andammonium fluoride. Etching time ranges from 30 seconds to 24 hours,depending on the etching temperature and the composition and thicknessof the material to be etched.

[0054] Referring to FIG. 6, the logic starts at a block 30, in which adot pattern mask is formed on a suitable substrate. As noted above,silicon is a preferred substrate material. FIG. 7A shows a mask 52 thatis laid down on the upper surface of a silicon substrate 50. Mask 52incorporates a round orifice 56. Orifice 56 is located in a positionthat corresponds to a desired location for a fluid channel in amicroneedle that is being fabricated. Note that to fabricate an array ofmicroneedles, a plurality of orifices 56 would be formed on a largerportion of substrate 50, each orifice corresponding to the location of amicroneedle being fabricated on the substrate material. Regardless ofthe number of orifices 56 formed, the size (diameter) of the orifices inthe dot pattern mask are about the same as that of the fluid channels inthe finished microneedle array.

[0055] Mask 52 can be produced using standard photo-lithographictechniques, or using other masking techniques commonly used in thesemiconductor industry. It is anticipated that mask 52 will beconstructed by applying a layer of silicon dioxide onto siliconsubstrate 50, and then forming orifice 56 in the layer of silicondioxide at the desired location.

[0056] Once the dot pattern mask has been formed, the logic moves to ablock 32, and by etching the substrate where defined by orifice 56, asis illustrated in FIG. 7B, a fluid channel 58 is formed. Because thesubstrate is covered by the dot pattern mask in all areas except thoseareas defined by orifice 56, the only portion of the substrate that willbe etched is the portion corresponding to the location of orifice 56. Itis expected that a conventional bulk-machining etching process, such aswet etching using a potassium hydroxide (KOH) solution, can bebeneficially employed. In such an etching process, the mask layer ismuch more resistant to the chemical used for etching than the substrateis, thus the substrate will be completely etched before the mask isremoved. Preferably, the etching process will continue until thesubstrate has been etched completely through to form fluid channel 58,which passes completely through the microneedle and through thesupporting substrate. However, it should be noted that the etchingprocess could be controlled to a particular depth, if a fluid channelthat does not completely pass through a substrate material is desired.Because the purpose of the fluid channel is to provide a fluid pathbetween the tip of the microneedle and either a fluid supply or a fluidreceiving reservoir (not shown here, see FIGS. 9 and 11), if the etchingprocess does not completely etch through the substrate, an additionalstep would be required to complete the desired fluid path. It shouldalso be noted that the RIE etching process described above can also beemployed to etch the silicon substrate, while leaving the silicon oxidelayer intact. Those of ordinary skill in the art will recognize that aplurality of other etching techniques can be beneficially employed inthis step, and that the techniques noted above are simply exemplary of apreferred approach, and are not intended to be limiting on the scope ofthe present invention.

[0057] Once fluid channel 58 has been etched through the substrate, thelogic proceeds to a block 34, and the dot pattern mask is removed.Removal of the dot pattern mask is the reverse of the etching process,because a chemical that dissolves the mask faster than it dissolves thesubstrate is used. Such mask removal techniques are well known in theart. FIG. 7C illustrates the result of this step, in which dot patternmask 52, visible in FIGS. 7A and 7B, has been completely removed fromsilicon substrate 50.

[0058] The logic now proceeds to a block 36 in FIG. 6 and the fourthstep, which is the formation of a nitride pattern mask. FIG. 7Dillustrates this step, in which a nitride pattern mask 60 has beenformed on silicon substrate 50. Note the areas of silicon substrate 50in which no nitride pattern mask has been formed. Specifically, thenitride pattern mask is not formed on the internal surfaces of orifice58, on the undersurface of silicon substrate 50, or on shoulder areas 62and 64 around opening into fluid channel 58. In particular, note thatshoulder area 62 on one side of the fluid channel is much smaller thanshoulder area 64 on the opposite side. The significance of thedifference in size between shoulder area 62 and shoulder area 64 willbecome clear below, from the discussion of subsequent steps in thefabrication process. It should be noted that this difference in theshoulder areas enables the formation of the beveled non-coring tip inthe present invention. It is expected that a layer of silicon dioxidecan be beneficially employed to form nitride pattern mask 60.

[0059] Once the nitride pattern mask has been completed, the logicproceeds to a block 38, in which a nitride layer is grown in all areasthat have not been covered by nitride pattern mask 60. FIG. 7Eillustrates the result of the nitride layer growth step, in which anitride layer 66 is grown. Note that nitride layer 66 covers theundersurface of silicon substrate 50, shoulder areas 62 and 64, and thewalls of fluid channel 58. One method of growing nitride layer 66provides a 300-700 angstrom thick layer of nitride, using a low pressurechemical vapor deposition (LPCVD) of dichlorosilane (SiH₂Cl₂) in thepresence of ammonia (NH₃), at a pressure of about ½ Torr and at atemperature of about 820° C. Those of ordinary skill in the art willrecognize that other methods for fabricating nitride layer 66 can beemployed and that the above noted technique is simply exemplary of onepreferred approach, but is not intended to be limiting on the scope ofthe present invention.

[0060] After nitride layer 66 has been grown, the logic moves to a block40 in FIG. 6, in which nitride pattern 60 is removed to expose thoseportions of silicon substrate 50 not covered with nitride layer 66. FIG.7F illustrates silicon substrate 50, nitride layer 66, orifice 58, andshoulders 62 and 64. No mask or nitride layer covers areas 63 on theupper surface of silicon substrate 50. Areas 63 can be preferentiallyremoved by etching, without removing the portions of substrate 50covered by nitride layer 66. Note that nitride layer 66 at shoulders 62and 64 mimics the offset pattern defined in nitride mask 60 of FIG. 7D.

[0061] After nitride pattern 60 is removed, the logic moves to a block42 in FIG. 6, in which an anisotropic bevel etch is performed on areas63. FIG. 7G illustrates the result obtained after this seventh step inthe process. Those skilled in the art will understand that severaldifferent etching processes are available for use with siliconsubstrates. In particular, an anisotropic etch is characterized by theformation of sharp, angular boundaries. Anisotropic etching can be usedto form trenches or side walls that are angular in shape, as opposed tothe more rounded etching seen in an isotropic etching process. Inanisotropic etching, the side walls etch much more slowly than thesurface, resulting in sharp boundaries and enabling the formation ofhigh aspect ratio structures. Tetramethylammonium hydroxide(N,N,N-Trimethyl-methanaminium hydroxide, or TMAH) is one of severaletchants used to achieve anisotropic etching. Note that sharply defined,angular or beveled surfaces 68 have been formed into silicon substrate50 of FIG. 7G. It should be noted that an anisotropic etch is alsoreferred to as a “bevel” etch, while an isotropic etch is also referredto as a “rounding” etch.

[0062] The logic then moves to a block 42 in FIG. 6. In this block,nitride layer 66 is removed. As noted above, either RIE or wet chemicalprocesses can be used to preferentially remove nitride layer 66.Furthermore, those of ordinary skill in the art will recognize thatother methods of removing nitride layer 66 can alternatively beemployed. FIG. 7H illustrates the result obtained after removing thenitride layer.

[0063] Finally the logic proceeds to a block 44, which indicates that anisotropic rounding etch is performed. Note that because nitride layer 66has been removed, shoulders 62 and 64 are no longer protected. Thus, inthe isotropic etching process, a portion of silicon substrate 50 atshoulders 62 and 64 is removed, forming the non coring tip of themicroneedle, in accord with the present invention. As noted above,isotropic etching is characterized by forming rounded surfaces, such ascurved surface 70, as opposed to the more angular surfaces formed inanisotropic etching.

[0064]FIG. 7J illustrates microneedle 22a as fabricated using the stepsdescribed in FIGS. 6 and 7A-7I. A ratio of a height H to width W ofmicroneedle 22 a is less than 1:2. Note that the size and shape of theoriginal silicon substrate 50 in FIG. 7A can be manipulated to changethe ratio of height H to width W in finished microneedle 22 a of FIG.7J. A thicker substrate 50 in FIG. 7A will result in a microneedlehaving a greater height H in FIG. 7J. Manipulation of the anisotropicetching step of FIG. 7G will also effect height H in finishedmicroneedle 22 a. A short etch time will result in a smaller height H,while a longer etch time will result in a greater height H.

[0065] Applications of the Microneedle Array

[0066] Another aspect of the present invention is directed to the use ofa microneedle array, configured as discussed above, in a diagnosticdevice. FIG. 8 illustrates such as a handheld diagnostic device 80.Handheld diagnostic device 80 includes a housing 81, a display 82, akeyboard 84, and a diagnostic cartridge 86. Note that diagnosticcartridge 86 can be removed from handheld diagnostic device 80. Duringuse, diagnostic cartridge 86 is removed from handheld diagnostic device80 and placed in contact with a portion of the user's skin, for example,on an arm 88 of the user. As explained below, blood is drawn from apatient's or user's body by the diagnostic cartridge for analysis in thediagnostic device, when the diagnostic cartridge holding the patient'sblood is replaced in diagnostic device 80.

[0067] It will be noted that the terms “user” and “patient” are employedinterchangeably throughout this specification and the claims thatfollow. It should be understood that the present invention can beemployed my a user who is a medical practitioner to treat another personwho is a patient, or a user who is a patient can directly employ thepresent invention.

[0068]FIG. 9 illustrates additional functional elements of handhelddiagnostic device 80 that are not visible in the schematic view of FIG.8. A processor 85 is bi-directionally linked to a memory 87 and keypad84. Display 82 is controllably connected to processor 85. Removablediagnostic cartridge 86, when properly inserted into housing 81, iselectrically connected to processor 85, so that any data collected bydiagnostic cartridge 86 are communicated to processor 85, which isprogrammed to run diagnostic routine on the signals provided by thediagnostic cartridge and to display the results on display 82.Preferably, memory 87 includes both read only memory (ROM) in whichmachine instructions are stored that cause the processor to carry outthe diagnostic routine and display the results, and random access memoryelement (RAM) (neither type of memory separately shown). Memory 87 isbi-directionally coupled to processor 85.

[0069]FIG. 10 illustrates further details of diagnostic cartridge 86. InFIG. 10, a diagnostic microneedle array 96 is shown exploded fromdiagnostic cartridge 86 to enable details of microneedle array 96 to beviewed, although it should be understood that in its fully assembledstate, diagnostic microneedle array 96 is inserted into a cavity 92 ofdiagnostic cartridge 86. Diagnostic cartridge 86 includes a housing 90,a plurality of electrical conductors 94, and cavity 92.

[0070] Diagnostic microneedle array 96 includes a silicon substrate 100,onto which a plurality of microneedles 98 are formed. Note that eachmicroneedle 98 has an associated fluid channel 106 that passescompletely through substrate 100 as well as through the microneedle. Asshown in FIG. 10, microneedles 98 are disposed on a bottom side ofsubstrate 100. On an upper side of substrate 100, a sensor 104 and aplurality of electrical contacts 102 are disposed. Sensor 104 andelectrical contacts 102 can be discrete components that are added ontosubstrate 100, but preferably, electrical contacts 102 and sensor 104are formed using semi-conductor fabrication techniques onto the oppositeside of silicon substrate 100 from microneedles 98. Electrical contacts102 are positioned so as to contact electrical conductors 94 withinhousing 90. The configuration employed for sensor 104 is a function ofthe type of diagnostic procedure that diagnostic cartridge 86 isexpected to perform and can be changed based on an intended usage. Forexample, one type of sensor that responds to glucose will be employed todetermine the blood-sugar of a diabetic patient. Thus, a person havingdiabetes could employ handheld diagnostic device 80 and a diagnosticcartridge 86 designed to monitor the blood sugar level (measured inmilligrams of glucose per 100 milliliters of blood).

[0071]FIG. 10 further illustrates a fluid reservoir 108 associated withdiagnostic microneedle array 96. In one embodiment, fluid reservoir 108is defined by the walls of cavity 92 in housing 90. In otherembodiments, fluid reservoir 108 is defined by a separate plastichousing mounted on silicon substrate 100 and sized to fit within cavity92.

[0072]FIG. 11 illustrates a side elevational view of diagnosticmicroneedle array 96. Fluid channels 106 pass completely through bothsubstrate 100 and microneedles 98. Fluid (such as a user's blood) isdrawn up through these orifices into fluid reservoir 108 when thediagnostic cartridge is applied to the user's skin, as shown in FIG. 8.The fluid contacts sensor 104, and the electrical signals from thesensor are transmitted along electrical leads 102, which connect toelectrical conductors 94 in diagnostic cartridge 86 when the diagnosticcartridge is inserted into cavity 92 of diagnostic cartridge 86.

[0073] In operation, a user will grasp diagnostic cartridge 86 and placeit with microneedles 98 of diagnostic microneedle array 96 disposedadjacent the user's skin. The user would apply gentle pressure todiagnostic cartridge 86, enabling the microneedles 98 to pierce theuser's dermal layer. A small volume of the user's blood would be drawnthrough fluid channels 106 into fluid reservoir 108. As the user's bloodcontacts sensor 104, electrical signals indicative of the parametersdetermined by sensor 104 are transferred from electrical contacts 102,to electrical conductors 94. The user then returns diagnostic cartridge86 to handheld diagnostic device 80, and electrical conductors 94connect to corresponding electrical contacts in the handheld diagnosticdevice, thereby transferring the sensor signal and the data they conveyto processor 85. The signals provided to processor 85 are processedaccording to the machine instructions stored within memory 87. Resultsare displayed to a user via display 82. The user can employ keypad 84 toenter patient specific data that processor 85 may require to properlyprocess the sensor signal data.

[0074]FIG. 12 illustrates a handheld drug delivery unit 110 thatincludes many of the same components of diagnostic unit 80, which isshown in FIG. 8. It is expected that the same handheld unit will be usedfor both the diagnostic unit and the drug delivery unit. Handheld drugdelivery unit 110 includes a housing 111, a display 114, a keypad 112,and a medicinal fluid supply 116 (which replaces diagnostic cartridge 86in diagnostic unit 80 to provide handheld drug delivery unit 110). Afluid line 118 connects medicinal fluid supply 116 to a deliverycartridge 124, and an electrical line 120 connects handheld drugdelivery system 110 to the delivery cartridge. A user will positiondelivery cartridge 124 so that it is disposed on the dermal layer(delivery cartridge 124 is illustrated disposed on an arm 122 of a useror patient) at a location to which the medicinal fluid is to bedelivered.

[0075]FIG. 13 illustrates additional functional elements of handhelddrug delivery unit 110 and delivery cartridge 124 that are not visiblein the schematic view of FIG. 12. A processor 115 is connectedbi-directionally to a memory 117 and keypad 112. A display 114 is alsoconnected to processor 115, as is fluid supply 116. Memory 117 includesROM in which machine instructions are stored, and RAM. Deliverycartridge 124 includes a housing 126, a fluid reservoir 136 that is influid communication with fluid supply 116, and a transducer array 130that is electrically connected to processor 115. Delivery cartridge 124further includes a microneedle array 140 that is in fluid communicationwith fluid reservoir 136.

[0076]FIG. 14 illustrates a partially exploded view of a deliverycartridge 124 a. Delivery cartridge 124 a includes an additional elementnot present in delivery cartridge 124, which is a spring assembly 132that produces a biasing force used to drive microneedle array 140 into adermal layer with a force sufficient to enable microneedles 144 topierce the patient's or user's dermal layer. FIG. 14 also illustratesdetails showing how transducer array 130 is electrically coupled tohandheld drug delivery system 11O, and how fluid reservoir 136 isconnected in fluid communication with handheld drug delivery system 110.Delivery cartridge 124 a includes electrical contacts 128, which connectultrasonic transducer 130 to electrical line 120. The electrical line isconnected to processor 115 of handheld drug delivery system 110. A fluidpassage 138 is in fluid communication with fluid reservoir 136 and alsoin fluid communication with a fluid line 118 that connects with fluidsupply 116 of handheld drug delivery system 110.

[0077] Spring assembly 132 is mounted on an upper portion of housing126, directly over fluid chamber 136. Microneedle array 140 is designedto fit within fluid chamber 136. FIG. 12 shows microneedle array 140exploded away from delivery cartridge 124 a so that details relating tomicroneedle array 140 can more clearly be seen; however, the microneedlearray is designed to be mounted within housing 126 under normalcircumstances. Microneedle array 140 includes a silicon substrate 146 onwhich the plurality of microneedles 144 are formed. A plurality oforifices 142 pass completely through substrate 146 as well asmicroneedles 144. As noted above, other materials, such as germanium,can be used for the substrate.

[0078]FIG. 15 illustrates further details of microneedle array 140. Inthis view, orifices 142 can clearly be seen passing completely throughsubstrate 146 and microneedles 144. A plurality of springs 148 connectsubstrate 146 to spring assembly 132 and are adapted to apply a biasingforce that enables the microneedles to pierce the dermal layer, when thesprings are compressed and then suddenly released to expand, applying abiasing force directed against the microneedle array, while themicroneedle array is in contact with a user's skin. Fluid chamber 136,fluid passage 138, and orifices 142 cooperate to deliver a medicinalfluid to a user. Note that FIG. 15 illustrates microneedle array 140 andsprings 148 in an extended position.

[0079] In an alternative embodiment that does not include springassembly 132 and springs 148, microneedle array 140 is instead fixedwithin the delivery cartridge, and the delivery cartridge positionedwith the microneedles disposed against the user's dermal layer. Thepenetration of the user's dermal layer can then be achieved by merelyapplying sufficient manual pressure against delivery cartridge 124.

[0080]FIG. 16 illustrates a microneedle element 150 that includes a flowsensor 156 and a flow control valve 158. Microneedle element 150 can beused in place of microneedle array 140 in delivery cartridge 124 or 124a. Microneedle element 150 includes a substrate 141, a fluid channel143, and microneedle 145. While for simplicity, only a singlemicroneedle and orifice are illustrated, it should be understood that aplurality of microneedles and fluid channel can be beneficiallyincorporated into microneedle element 150. If a plurality ofmicroneedles and fluid channels are included, then either a plurality ofsensors and flow control valves (one for each microneedle) should beincluded, or sensor 156 and flow control valve 158 should be sizedsufficiently large to effect the flow of fluids in the range requiredfor the plurality of microneedles. For instance, if microneedle element150 is incorporated into an array of microneedles, then a single sensorand a single flow control valve having widths as least as wide as awidth of the array may be required.

[0081] Flow sensor 156 can be separately fabricated and attached tosubstrate 141, or traditional semi-conductor manufacturing techniquescan be used to fabricate flow sensor 156 on substrate 141. Preferably,housing 152 is fabricated from silicon as well, such that traditionalsemi-conductor manufacturing techniques can be used to fabricate flowcontrol valve 158. However, other manufacturing techniques may beemployed. An orifice 154 is disposed in an upper portion of housing 152to enable a medicinal fluid to enter microneedle element 150.

[0082]FIG. 17 provides additional detail of an embodiment of fluidsupply 116. As illustrated in FIG. 12, fluid supply 116 is disposed inhandheld delivery system 110. It is envisioned that fluid supply 116 canbe a disposable unit that is replaced once the medicinal fluid containedwithin is fully dispensed. Fluid supply 116 preferably includes an upperhousing 166, a plurality of electromechanical actuators 164, aself-sealing elastomeric membrane 162, and a sub-micron filter 168.

[0083] Electrochemical actuators are know in the art. Such actuatorsapply a voltage to a fluid in a sealed chamber. The voltage causes thefluid to generate a gas, which in turn increases the pressure within thechamber, thereby providing the desired mechanical actuation force. Whenthe voltage is removed, the gas is reabsorbed by the fluid, which canthen be electrically stimulated to repeat the process, as desired. Someelectrochemical actuators employ a fluid, which reversibly oxidizes inresponse to the application of a voltage, and when the voltage isremoved the corresponding reduction reaction returns the fluid to itsoriginal state.

[0084] To fill fluid supply 116, a syringe (not shown) piercesself-sealing elastomeric membrane 162, so that the medicinal fluid canbe injected from the syringe into an interior of fluid supply 116. Whenactuators 164 are providing no driving pressure to the fluid within theinterior of fluid supply 116, the fluid will not pass through sub-micronfilter 168. However, when an appropriate actuation pressure is providedby actuators 164, the fluid will pass through sub-micron filter 168 andinto chamber 170, flowing into fluid line 118.

[0085] In general, when a user is ready to use drug delivery system 110,the first step would be to insure that the desired medicinal fluidsupply 116 is inserted into unit 110. It is anticipated that a singleuser might use drug deliver system 110 to administer more than one typeof medicinal fluid, and that such a user would have a plurality ofmedicinal fluid supplies 116 containing different types of medicinalfluids. The user would then enter user data, such as the desireddelivery rate, using keypad 112. Using such information, processor 115can control the delivery rate, by controlling the fluid flow from fluidsupply 116. In a preferred embodiment, processor 115 controls thepressure delivered by actuators 164, to provide the desired fluiddelivery rate. The user will position delivery cartridge 124 on adesired portion of the user's dermal layer. Generally, this portion willbe on the arm of the user, or patient, although other portions of thepatient's dermal layer can be used for transcutaneously infusingmedicinal fluids.

[0086] With reference to FIG. 15, an ultrasonic transducer array 130 isincluded to enable a particularly desirable target location to beselected. Ultrasonic transducer 130 transmits ultrasonic signals intothe patient's body, receives the reflected signals, producingcorresponding signals indicative of the internal structure, and conveysthe signals to handheld delivery system 110 via electrical line 120.Processor 115 monitors the signals from transducer array 130, and once adesired location has been achieved as the user moves delivery cartridge124 across the user's skin, processor 115 causes display 114 to alertthe user that delivery cartridge 124 is in a desired position. At thispoint, either by using a light pressure to force microneedles 144through the dermal layer, or by employing springs 148 to drive themicroneedles through the dermal layer, delivery cartridge 124 begins todeliver a controlled amount of medicinal fluid to the patient across thedermal barrier. The appropriate position can be determined based uponthe characteristics of the patient's skin, or based upon the internalcondition of the patient's body. For example, it may be appropriate touse the ultrasonic transducer to determine a position on the dermallayer that is adjacent injured internal soft tissue, so that a painkiller and/or anti-inflammatory can be injected into patient at thatsite using delivery cartridge 124.

[0087] Although the present invention has been described in connectionwith the preferred form of practicing it, those of ordinary skill in theart will understand that many modifications can be made thereto withinthe scope of the claims that follow. Accordingly, it is not intendedthat the scope of the invention in any way be limited by the abovedescription, but instead be determined entirely by reference to theclaims that follow.

The invention in which an exclusive right is claimed is defined by thefollowing:
 1. A hollow microneedle comprising: (a) a generallyconical-shaped body having a beveled, non-coring tip, said tip beingsharp and able to pierce tissue; (b) said conical body further having abroad base formed of a substrate at an opposite end from the tip; and(c) a fluid channel extending through the conical-shaped body, providingfluid communication between said broad base and said tip.
 2. The hollowmicroneedle of claim 1, wherein a height of the microneedle, which isdefined as a distance from said broad base to said tip, is within arange from about 50 μm to about 100 μm.
 3. The hollow microneedle ofclaim 1, wherein a height of each microneedle, which is defined as adistance from said broad base to said tip, is substantially less than awidth of said broad base.
 4. The hollow microneedle of claim 1, whereinsaid hollow microneedle comprises silicon.
 5. Apparatus for conveying afluid transcutaneously, comprising: (a) a substrate, said substratecomprising at least one inlet, and a plurality of outlets in fluidcommunication with said at least one inlet; and (b) a plurality ofmicroneedles arranged in an array and extending substantially outwardlyfrom said substrate, each microneedle including: (i) a generallyconical-shaped body having a beveled, non-coring tip, said tip beingsharp and able to pierce tissue; (ii) said conical body further having abroad base formed of the substrate at an opposite end from the tip; and(iii) a fluid channel extending through the conical-shaped body,providing fluid communication between one of the outlets disposed saidbroad base is formed from the substrate and said tip.
 6. The apparatusof claim 5, wherein a height of each microneedle, which is defined as adistance from said broad base to said tip, is within a range from about50 μm to about 100 μm.
 7. The apparatus of claim 5, wherein a height ofeach microneedle, which is defined as a distance from said broad base tosaid tip, is substantially less than a width of said broad base.
 8. Theapparatus of claim 5, wherein at least one of said substrate and themicroneedles comprises silicon.
 9. The apparatus of claim 5, whereinsaid array of the microneedles is integrally formed from said substrate.10. A method of manufacturing a hollow microneedle, comprising the stepsof: (a) providing a substrate; (b) forming a fluid channel within saidsubstrate, such that said fluid channel passes through said substrate;and (c) removing a substantial portion of said substrate, therebyleaving a remainder, said remainder surrounding said fluid channel andbeing generally conical in shape, such that said fluid channel isgenerally disposed along a central axis of the conical shape.
 11. Themethod of claim 10, wherein the step of removing a substantial portionof said substrate comprises the step of beveling a tip of said conicalshape.
 12. The method of claim 10, wherein the step of providing asubstrate comprises the step of providing a substrate comprising one ofsilicon and polysilicon.
 13. The method of claim 12, wherein the step offorming a fluid channel comprises the steps of: (a) forming a firstmask; (b) etching the substrate through an orifice formed in the firstmask to form said fluid channel; and (c) removing said first mask. 14.The method of claim 12, wherein the step of removing a substantialportion of said substrate comprises the steps of: (a) forming a secondmask; (b) depositing a nitride layer; (c) removing said second mask; and(d) etching said substrate to remove a substantial portion of saidsubstrate.
 15. The method of claim 14, wherein the step of etching saidsubstrate comprises the step of performing an anisotropic etch.
 16. Themethod of claim 14, wherein the step of etching said substrate comprisesthe steps of removing said nitride layer and performing an isotropicetch of the substrate.
 17. The method of claim 14, wherein the step ofetching said substrate comprises the steps of: (a) performing ananisotropic etch of the substrate; (b) removing said nitride layer; and(c) performing an isotropic etch of the substrate.
 18. A method ofmanufacturing an array of hollow microneedles, comprising the steps of:(a) providing a silicon substrate; (b) preparing a dotted mask on anupper surface of said silicon substrate, such that openings in saiddotted mask correspond to desired locations for said hollow microneedlesin the array; (c) etching said silicon substrate so as to form aplurality of fluid channels that extend substantially through saidsilicon substrate; (d) forming a nitride mask such that said nitridemask covers areas in which no nitride layer is desired; (e) forming anitride layer, such that said nitride layer is deposited on thesubstrate in the areas not covered by the nitride mask; (f) removingsaid nitride mask; (g) performing a bevel etch upon said substrate,thereby forming an array of blunt, angular microneedles; (h) removingsaid nitride layer; and (i) performing a rounding etch to round andsharpen said blunt angular microneedles, thereby completing said arrayof hollow microneedles.
 19. The method of claim 18, wherein the siliconsubstrate has a thickness that is substantially equal to a desiredheight of the hollow microneedles comprising said array.
 20. The methodof claim 11, wherein the step of providing a silicon substrate comprisesthe step of providing a silicon substrate having a thickness within arange from about 50 μm to about 100 μm.
 21. The method of claim 11,wherein in the array of blunt, angular microneedles, each microneedlehas a base and a height, and wherein a width of said base is at leastabout equal to said height.
 22. A minimally invasive diagnostic systemfor sampling and analyzing a biological fluid from a patient,comprising: (a) a handheld diagnostic unit comprising a housing, aprocessor, a display electrically coupled to said processor, a keypadelectrically coupled to said processor, and a memory electricallycoupled to said processor; (b) a disposable cartridge for obtaining asample of said biological fluid from a patient, said disposablecartridge comprising a housing and an array of microneedles; and (c) asensor that when in contact with the sample of the biological fluid,produces a signal indicative of a characteristic of said biologicalfluid, said sensor being adapted to electrically couple with saidprocessor to provide the signal to the processor for diagnosticprocessing.
 23. The minimally invasive diagnostic system of claim 22,wherein each microneedle of said array comprises: (a) a generallyconical-shaped body having a beveled, non-coring tip, said tip beingsharp and able to pierce tissue; (b) said conical body further having abroad base formed of a substrate at an opposite end from the tip; and(c) a fluid channel extending through the conical-shaped body, providingfluid communication between said broad base and said tip.
 24. Theminimally invasive diagnostic system of claim 23, wherein a height ofthe microneedle, which is defined as a distance from said broad base tosaid tip, is within a range from about 50 μm to about 100 μm.
 25. Theminimally invasive diagnostic system of claim 23, wherein a height ofeach microneedle, which is defined as a distance from said broad base tosaid tip, is substantially less than a width of said broad base.
 26. Theminimally invasive diagnostic system of claim 23, wherein said array ofmicroneedles comprises silicon.
 27. The minimally invasive diagnosticsystem of claim 22, wherein said memory stores machine instructions thatcause the processor to perform a diagnostic procedure using the signal,and indicate a result of the diagnostic procedure on the display. 28.The minimally invasive diagnostic system of claim 27, wherein saiddiagnostic procedure determines a level of glucose in said biologicalfluid.
 29. The minimally invasive diagnostic system of claim 22, whereinsaid housing comprises a receptacle having a size and shape adapted toreceive said disposable cartridge, and when said cartridge is insertedinto said receptacle, said sensor is electrically coupled to saidprocessor.
 30. The minimally invasive diagnostic system of claim 22,wherein said sensor is disposed in said disposable cartridge.
 31. Theminimally invasive diagnostic system of claim 30 wherein said array ofmicroneedles comprises a silicon substrate having a first surface onwhich said array of microneedles is formed, and a second surface onwhich said sensor is formed.
 32. The minimally invasive diagnosticsystem of claim 22, wherein said sensor is disposed in said housing. 33.A minimally invasive drug delivery system for transdermally delivering amedicinal fluid into a patient, comprising: (a) a handheld control unitcomprising a housing, a processor, a display electrically coupled tosaid processor, a keypad electrically coupled to said processor, amemory electrically coupled to said processor; a medicinal fluidreservoir, a medicinal fluid outlet in fluid communication with saidmedicinal fluid reservoir, and an actuator that develops pressure toforce the medicinal fluid from the medicinal fluid reservoir and throughthe medicinal fluid outlet for infusion into the patient, said actuatorbeing electrically coupled to and controlled by the processor; (b) adisposable cartridge, said disposable cartridge comprising a housing,and an array of microneedles through which the medicinal fluid isinfused into the patient; and (c) a fluid line having a distal end and aproximal end, said proximal end being connected to said medicinal fluidoutlet, and said distal end being coupled with said disposable cartridgeto provide fluid communication between the medicinal fluid outlet andthe disposable cartridge.
 34. The minimally invasive drug deliverysystem of claim 33, wherein each individual microneedle of said arraycomprises: (a) a generally conical-shaped body having a beveled,non-coring tip, said tip being sharp and able to pierce tissue; (b) saidconical body further having a broad base formed of a substrate at anopposite end from the tip; and (c) a fluid channel extending through theconical-shaped body, providing fluid communication between said broadbase and said tip.
 35. The minimally invasive drug delivery system ofclaim 34, wherein a height of the microneedle, which is defined as adistance from said broad base to said tip, is within a range from about50 μm to about 100 μm.
 36. The minimally invasive drug delivery systemof claim 34, wherein a height of each microneedle, which is defined as adistance from said broad base to said tip, is substantially less than awidth of said broad base.
 37. The minimally invasive drug deliverysystem of claim 34, wherein a ratio of a height of each microneedle,which is defined as a distance from said broad base to said tip, to awidth of said broad base ranges between about 1:1 to about 1:2.
 38. Theminimally invasive drug delivery system of claim 33, (a) furthercomprising a data cable, said data cable having a proximal end and adistal end, said proximal end of the data cable being connected to saidhandheld control unit, such that said data cable is electrically coupledto said processor, said distal end of the data cable being electricallycoupled to said disposable cartridge; and (b) said disposable cartridgefurther including an ultrasonic transducer array that produces anultrasonic signal directed into target region within a body of a patientand receives a reflected ultrasonic signal from within the body of thepatient, producing an output signal indicative of a condition of thetarget region, said ultrasonic transducer array being electricallycoupled to said data cable through which the output signal is conveyed,said processor responding to the output signal and indicating to a useron the display that said disposable cartridge is disposed adjacent to adesired region within the body of the patient.
 39. The minimallyinvasive drug delivery system of claim 33, wherein said disposablecartridge further comprises at least one spring element that applies abiasing force to said array of microneedles, causing the microneedles topenetrate a dermal layer of a patient.
 40. The minimally invasive drugdelivery system of claim 38, wherein said disposable cartridge furthercomprises a flow sensor for monitoring a flow rate of said medicinalfluid and producing a flow signal indicative thereof, said flow sensorproviding the flow signal to the processor through the data cable. 41.The minimally invasive diagnostic system of claim 40, wherein said arrayof microneedles comprises a silicon substrate having a first surface onwhich said array of microneedles is formed, and a second surface onwhich said flow sensor is formed.
 42. The minimally invasive drugdelivery system of claim 33, wherein said disposable cartridge furthercomprises a valve for controlling a flow of said medicinal fluid into apatient.
 43. The minimally invasive drug delivery system of claim 33,wherein said medicinal fluid reservoir comprises a housing, a selfsealing elastomeric membrane defining one portion of said medicinalfluid reservoir, and a sub-micron filter that prevents said medicinalfluid from exiting said medicinal fluid reservoir until said actuatordevelops a pressure that acts on said medicinal fluid.
 44. The minimallyinvasive drug delivery system of claim 33, wherein the medicinal fluidreservoir is removable from the handheld control unit and replaceablewith a disposable diagnostic cartridge for use in obtaining a sample ofa biological fluid from a patient, said disposable cartridge comprisinga housing and an array of microneedles, a sensor being provided thatwhen in contact with the sample of the biological fluid, produces asignal indicative of a characteristic of said biological fluid, saidsensor being adapted to electrically couple with said processor toprovide the signal to the processor for diagnostic processing.